Treatment of canine leishmaniosis: An update.

PDF
Published: Jan 31, 2018
DOI: https://doi.org/10.12681/jhvms.15411
M. N. SARIDOMICHELAKIS (Μ. Ν. ΣΑΡΙΔΟΜΙΧΕΛΑΚΗΣ)
Clinic of Companion Animal Medicine, Faculty of Veterinary Medicine, A.U.T.
A. F. KOUTINAS (Α.Φ. ΚΟΥΤΙΝΑΣ)
Clinic of Companion Animal Medicine, Faculty of Veterinary Medicine, A.U.T.
M. E. MYLONAKIS (Μ.Ε. ΜΥΛΩΝΑΚΗΣ)
Clinic of Companion Animal Medicine, Faculty of Veterinary Medicine, A.U.T.
Abstract

The drugs, currently recommended in the treatment of canine leishmaniosis, include meglumine antimonate, allopurinol, paromomycin (aminosidine) and amphotericin B. With the exception of meglumine antimonate, where an optimal dosage has been established (75 mg/Kg BW, every 12 hours, SC), that of allopurinol (10-20 mg/Kg, BW BID, per os), paromomycin (5-10 mg/Kg BW BID, SC or IM) and amphotericin Β (0,5-0.8 mg/Kg BW, 2-3 times weekly, IV, up to a total dose of 8-15 mg/Kg BW), still remains empirical. Although the side effects are relatively few and harmless with the use of meglumine antimonate and allopurinol, they are often life-threatening with paromomycin (ototoxic, nephrotoxic) or amphotericin Β(nephrotoxic). Although the current antileishmanial medications result in the clinical cure of the affected animals and may decrease the contamination potential of sandflies, a parasitological cure is not but occasionally achieved. Therefore, prolonged administration of allopurinol, with or without the intermittent use of meglumine antimonate, is recommended in an attempt to avoid clinical flare-ups. However, repeated cycles of treatment with meglumine antimonate may lead to the emergence of resistant Leishmania spp clones. Withdrawal of medication is justified only when two PCR tests, done on bone marrow samples, 6-months apart, are negative. In the future, the use of cytokines produced by activated Th-1 cells (INF-γ, IL-2, IL-12), may resolve the controversial issue of permanent cure in the dog.

Article Details
  • Section
  • Special Article
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with this journal agree to the following terms:

· Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution Non-Commercial License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

· Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g. post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

· Authors are permitted and encouraged to post their work online (preferably in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.

Downloads
Download data is not yet available.
References
Bettini S, Gradoni L. Canine leishmaniasis in the Mediterranean area and its implications for human leishmaniasis. Insect Sci Appi, 1986,7: 241-245.
Ashford RW, Bettini S. Ecology and epidemiology: Old World. In: W Peters, R Killick-Kendrich (Editors), The Leishmaniasis in Biology and Medicine. Vol I. Biology and Epidemiology. Academic Press, London, 1987, pp. 365-424.
World Health Organization. Control of Leishmaniases. Technical Report Series No 793. WHO, Geneva, 1990.
Ferrer L. Leishmaniasis. In: RW Kirk, JD Bonagura (Editors), Current Veterinary Therapy XI - Small Animal Practice. WB Saunders, Philadelphia, 1992, pp. 266-270.
Martinez-Cruz MS, Martinez-Moreno A, Martinez-Moreno FJ, Hernadez-Rodriguez S. Epidemiologia de leishmaniasis canina en la provincia de Cordoba. Rev Iber Parasitol, 1993, 51: 49-59.
Zaffaroni E, Rubaudo L, Lanfranchi P, Migrone W. Epidemiological patterns of canine leishmaniasis in Western Liguria (Italy). Vet Parasitol, 1999,81:11-19.
Berrahal f, Mary G, Roze M, Berenger A, Escoffier K, Lamouroux D, Dunan S. Canine leishmaniasis: identification of asymptomatic carriers by polymerase chain reaction and immunobloting. Am J Trop Med Hyg, 1996,55: 273-277.
Cabrai Μ, Ο' Grady G, Alexander G. Demonstration of Leishmania specific cell mediated and humoral immunity in asymptomatic dogs. Parasit Immunol, 14: 531-539.
Martinez-Moreno A, Moreno T, Martinez-Moreno FJ, Acosta I, Hernadez S. Humoral and cell-mediated immunity in natural and experimental canine leishmaniasis. Vet Immunol Immunopathol, 1995,48: 209-220.
World Health Organization. The Leishmaniases. Technical Report Series No 701. WHO, Geneva, 1984.
Jaffe CL. Prospectives for a vaccine against canine leishmaniasis. Summaries of Presentations at the International Canine Leishmaniasis Forum, 1999, pp. 9.
Baneth G, Dark G, Keren-kornblatt E, Sekeles E, Adini I, Eisenberger CL, Schnur LF, King R, Jaffe CL. Emergence of visceral leishmaniasis in central Israel. Am J Trop Med Hyg, 1998,59: 722-725.
Slappendel RJ, Ferrer L. Leishmaniasis. In: CE Greene (Editor), Infectious Diseases of the Dog and the Cat, 2nd edition. WB Saunders, Philadelphia, 1998, pp. 450-458.
Kontos VI, Koptopoulos GS, Haralabidis STh, Spais AG. Studies on the role of the ground squirrel (Citellus citellus) in the epidemiology of leishmaniasis. In: DT Hart (Editor), Leishmaniasis. The Current Status and New Strategies for Control. Plenum Press, New York, 1989, pp. 83-87.
Ashford DA, Bozza M, Freire M, Miranda JC, Sherlock I, Eutalio C, Lopes U, Fernandes O, Degrave W, Barker RHJr, Badarq R, David JR. Comparison of the polymerase chain
reaction and serology for the detection of canine visceral leishmaniasis. Am J Trop Med Hyg, 1995,53: 251-255.
Χαραλαμπίδης Σ. Λεϊσμανίωση, τοξοπλάσμωση, υδατίδωση-εχινοκόκκωση. Προκατάληψη και πραγματικότητα. Ι. Σπλαγχνική λεϊσμανίωση. Anima, 1997,5: 24-31.
Miles ΜΑ, Vexenat JA, Furtado Campos JH, Fonseca de Castro JA. Canine leishmaniasis in Latin America: Control strategies for visceral leishmaniasis. Summaries of Presentations at the International Canine Leishmaniasis Forum, 1999, pp. 6-7.
Dietze R, Barros GB, Teixeira L. Effect of elimination of seropositive canines on the transmission of visceral leishmaniasis in Brazil. Clin Infect Pis, 1997,25:1240-1242.
Killick-Kendrick R, Killick-Kendrick M. The biology of the sandfly vectors of the Mediterranean canine leishmaniasis. Summaries of Presentations at the International Canine Leishmaniasis Forum, 1999, pp. 10.
Gradoni L, Maroli M, Gramiccia M, Mancianti F. Leishmania infantum infection rates in Phlebotomus perniciosus fed on naturally infected dogs under antimonial treatment. Med Vet Entomol, 1987,1: 339-342.
Killick-Kendrick R, Killick-Kendrick M, Focheux C. Protection of dogs from bites of phlebotominae sandflies by deltamethrin collars for control of canine leishmaniasis. Med
Vet Entomol, 1977,11:105-111.
Noli C. Canine leishmaniasis. Waltham Focus, 1999,9:16-24.
Slappendel RJ. Canine leishmaniasis. A review based on 95 cases in the Netherlands. Vet Quart, 1988,10:1-16.
Koutinas AF, Polizopoulou ZS, Saridomichelakis MN, Argyriadis D, Fytianou A, Pleuraki K. Clinical considerations on canine visceral leishmaniasis (CVL) in Greece: a
retrospective study of 158 spontaneous cases. J Am Anim Hosp Assoc, 1999,35: 375-383.
Lamothe J, Ribot X. Leishmaniose canine: du diagnostic au traitement. Bull Soc Vet Prat France, 1996,80:197-222.
Pinelli E, Gonzalo RM, Boog CJP, Rutten VPMG, Gebhard D, Del Real G, Ruitenberg EJ. Leishmania infantum-specific T-cell lines that lyse infected macrophages in a major
histocompatibility complex-restricted manner. Europ J Immunol, 1995,25:1594-1600.
Pinelli E, van der Kaaij SV, Rutten VPMG, Ruitenberg EJ. Cytokines in a canine model of visceral leishmaniasis. Strategies for the induction of protective immunity. Immunol Letters, 1997,56:144.
Vouldoukis I, Drapier JC, Nussler AK, Tselentis Y, Da Silva OA, Gentilli M, Mossalayi DM, Monjour L, Dugas B. Canine visceral leishmaniasis: successful chemotherapy induces macrophage antileishmanial activity via the L-arginine nitric oxide pathway. Antimicrob Agents Chemother, 1996,40:253-256.
Ferrer L. Leishmaniasis: update in diagnosis and therapy. Proc 14th Ann Congr ESVD-ECVD, 1997, pp. 33-36.
Liste F, Gascon M. Allopurinol in the treatment of canine visceral leishmaniasis. Vet Ree, 1995,137: 23-24.
Vercammen F, De Deken R, Kageruka P. First evaluation of the use of allopurinol for the treatment of canine leishmaniasis. Vlaams Diergen Tijdschr, 1995,64: 208-214.
Ginel PJ, Lucena R, Lopez R, Molleda JM. Use of allopurinol for maintenance of remission in dogs with leishmaniasis. J Small Anim Pract, 1998,39: 271-274.
Berman JD. Chemotherapy for leishmaniasis: biochemical mechanisms, clinical efficacy and future strategies. Rev Infect Pis, 1988,10: 560-586.
Chapman WLJr, Hanson WL, Waits VB, Kinnamon KE. Antileishmanial activity of selected compounds in dogs experimentally infected with Leishmania donovani. Rev Inst
Med Trop Sao Paulo, 1979,21:189-193.
Tassi Ρ, Ormas Ρ, Madonna M, Carli S, Bellori C, De Natale G, Marcotrigiano GO. Pharmacokinetics of N-methylglucamine antimonate after intravenous, intramuscular and
subcutaneous administration in the dog. Res Vet Sci, 1994,56: 144-150.
Valladares JE, Riera C, Alberola J, Gallego M, Portus M, Cristofol C, Franquelo C, Arboix M. Pharmacokinetics of meglumine antimonate after administration of a multiple
dose in dogs experimentally infected with Leishmania infantum. Vet Parasitol, 1998,75: 33-40.
Martinez S, Looker DL, Berens RL, Marr JJ. The synergistic action of pyrazolopyrimidines and pentavalent antimony against Leishmania donovani and L. braziliensis. Am J Trop Med Hyg, 1988, 39: 250-255.
Bellori C, Ceci L, Carli S, Tassi Ρ, Montesissa C, de Natale G, Marcotrigiano G, Ormas P. Disposition of antimony and aminosidine in dogs after administration separately and together: implications for therapy of leishmaniasis. Res Vet Sci, 1995,58:123-127.
Ferrer L, Kramer L. Workshop report 7.13-Leishmaniasis. In: KW Kwochka, T. Willemse, C von Tscharner (Editors), Advances in Veterinary Dermatology Vol 3. Butterworth- Heinemann, Oxford, 1998, pp. 414-416.
Valladares JE, Alberola J, Esteban M, Arboix N. Disposition of antimony after the administration of N-methylglucamine antimonate to dogs. Vet Ree, 1996,138:181-183.
Denerolle P, Bourdoiseau C. Combination allopurinol and antimony treatment versus antimony alone and allopurinol alone in the treatment of canine leishmaniasis (96 cases). J Vet Intern Med, 1999,13: 413-415.
Mancianti F, Gramiccia M, Gradoni L, Pieri S. Studies on canine leishmaniasis control. 1. Evolution of infection of different clinical forms of canine leishmaniasis following antimonial treatment. Trans Royal Soc Trop Med Hyg, 1988, 82: 566-567.
Slappendel RJ, Teske E. The effect of intravenous or subcutaneous administration of meglumine antimonite (Glucantime(r)) in dogs with leishmaniasis. A randomized clinical trial. Vet Quart, 1997,19:10-13.
Berenger A. A proposed schedule of treatment promising long term cure for canine leishmaniasis. Prat Med Chir Anim Comp, 1988,23:111-119.
Ferrer LM. Leishmaniasis. Proc XVI World Congr WSAVA, 1991, pp. 52-54.
Alvar J, Molina R, San Andres M, Tesouro M, Nieto J, Vitutia M, Gonzales F, San Andres MD, Boggio J, Rodriguez F, Sainz A, Escacena C. Canine leishmaniasis: clinical,
parasitological and entomological follow-up after chemotherapy. Ann Trop Med Parasitol, 1994,88: 371-378.
Von Lindner T. Kombinationstherapie der hundeleishmaniose (HL) mit megluminantimoniat und allopurinol ambeispiel einer tecklhundin. Tierarztl Umschau, 1995, 50:797-798.
Roura X, Sanchez A, Ferrer L. Diagnosis of canine leishmaniasis by a polymerase chain reaction technique. Vet Ree, 1999,144: 262-264.
Roura X, Sanchez A, Ferrer L Follow-up of Leishmania infected dogs after treatment using a PCR technique. Proc 14th Ann Congr ESVD-ECVD, 1997, pp.171.
Mendez CL. Results of a triple treatment in dogs with leishmaniasis. Proc 16th Ann Congr ESVD-ECVD, 1999, pp. 124
Chylay JD, Fleckenstein L, Smith DH. Pharmacokinetics of antimony during treatment of canine visceral leishmaniasiswith sodium stibogluconate or meglumine antimonate. Trans Royal Soc Trop Med Hyg, 1988,82: 69-72.
Al-Jaser M, El-Vazigi A, Croft SL. Pharmacokinetics of antimony in patients treated with sodium stibogluconate for cutaneous leishmaniasis. Pharm Res, 1995,12:113-116.
Olliaro PL, Bryceson ADM. Practical progress and new drugs for changing patterns of leishmaniasis. Parasitol Today, 1999, 9: 323-328.
Croft SL, Urbina JA, Brun R. Chemotherapy of human leishmaniasis and trypanosomiasis. In: G Hide, JC Mottram, GH Coombs, PH Holmes (Editors), Trypanosomiasis and Leishmaniasis. Biology and Control. Cab International, Wallingford, 1997, pp. 245-257.
Grogl M, Oduola AM, Corderò LD, Kyle DE. Leishmania spp: development of pentostam-resistant clones in vitro by discontinuous drug exposure. Exp Parasitol, 1989,69: 78-90.
Gramiccia M, Gradoni L, Orsini S. Decreased sensitivity to meglumine antimonate (Glucantime) of Leishmania infantum isolated from dogs after several courses of drug treatment. Ann Trop Med Parasitol, 1992,86: 613-620.
Faraut-Garambelli F. Chimioresistance des leishmanies. Etude de la sensibilité de Leishmania infantum a la N-methylglucamine. Med Armées, 1994,22: 69-71.
Grogl M, Thomason T, Franke ED. Drug resistance in leishmaniasis: its implications in systemic chemotherapy of cutaneous and mucocutaneous disease. Am J Trop Med Hyg, 1992,47:117-126.
Huss BT, Ettinger SJ. Visceral leishmaniasis, Rocky Mountain spotted fever and von Willebrand's disease in a giant Schnauzer. J Am Anim Hosp Assoc, 1992,29: 221-225.
Denerolle P. Leishmaniose canine: difficulté du diagnostic et du traitement. Prat Med Chirurg Anim Comp, 1996,31:137-145.
Giauffret A, Sanchis R, Vitu C. Les examines de laboratoire dans la leishmaniose canine. I. Application au diagnostic, au prognostic et au contrôle dans la maladie naturelle. Rev Med
Vet, 1976,127: 913-930.
Bergeaud P. L' apport de la corticotherapie dans le traitement de certaines formes de leishmaniose canine: résultats sur une serie de quarante-trois cas. Prat Med Chirurg Anim Comp, 1988, Suppl, 5:121-127
Deplazes P, Arnold P, Skaggs J, Gessler M. Parasitologische und immunologische Verlaufskontrollen wahrend und nach Chemotherapie der leishmaniose des hundes. Schweiz Arch Tierheilk, 1992,134: 85-93.
Neogy AB, Vouldoukis I, da Costa JM, Monjour L. Exploitation of parasite derived antigen in therapeutic success against canine visceral leishmaniosis. Veterinary Group of Lupino. Vet Parasitol, 1994,54: 367-373.
Oliva G, Cortese L, Ciaramella Ρ, DeLuna R. Trattamento terapeutico della leishmaniosi del cane. Veterinaria, 1996,10:115-127.
Chapman WL, Hanson WL, Alving CR, Hendricks LD. Antileishmanial activity of liposome-encapsulated meglumine antimonate in the dog. Am J Vet Res, 1984,45:1028-1030.
Valladares JE, Freixas J, Alberola J, Franquelo C, Cristofol C, Arboix M. Pharmacokinetics of liposome – encapsulated meglumine antimonate after intramuscular and subcutaneous administration in dogs. Am J Trop Med Hyg, 1997, 57: 403-406.
Slappendel RG, Greene CE. Leishmaniasis. In: CE Green (Editor) Infectious diseases of the dog and the cat. WB Saunders, Philadelphia, 1990, pp. 760-777.
Reusch C, Reiter I. Imported leishmaniosis in dogs: trials using Na-stilbogluconate (Pentostam) with regard to treatment, diagnosis and clinical signs. Vet Practice, 1987,15:
-310.
Poli A, Sozzi S, Guidi G, Bandinelli Ρ, Mancianti F. Comparison of aminosidine (paromomycin) and sodium stibogluconate for treatment of canine leishmaniasis. Vet Parasitol, 1997,71: 263-271.
Nelson DJ, Bugge CJL, Elion GB, Berens RL, Marr JJ. Metabolism of pyrazolo (3,4-d) pyrimidines in Leishmania braziliensis and Leishmania donovani. J Biol Chem, 1979, 254: 3959-3964.
Marr JJ, Berens RL. Pyrazolopyrimidine metabolism in the pathogenic trypanosomatidae. Mol Biochem Parasitol, 1983, 7: 339-356.
Ling GV, Ruby AL, Harrold DR, Johnson DL. Xanthinecontaining urinary calculi in dogs given allopurinol. J Am Vet Med Assoc, 1991,198:1935-1940.
Plumb DC. Veterinary Drug Handbook, 2nd edition, Iowa State University Press, Ames, 1996.
Bartges JW, Osborne CA, Felice LJ, Unger LK, Chen M. Influence of allopurinol and two diets on 24 - hour urinary excretions of uric acid, xanthine, and ammonia by healthy
dogs. Am J Vet Res, 1995,56: 595-599.
Cavaliero T, Arnold P, Mathis A, Glaus T, Hofmann-Lehmann R, Deplazes P. Clinical, serologic and parasitologic follow-up after long-term allopurinol therapy of dogs naturally infected with Leishmania infantum. J Vet Intern Med, 1999,13: 330-334.
Arellano F, Sacristan JA. Allopurinol hypersensitivity syndrome: a review. Ann Pharmacother, 1993,27: 337-343.
Drayer DE. Pharmacologically active drug metabolites: therapeutic and toxic activities, plasma and urine data in man, accumulation in renal failure. Clin Pharmacokinet, 1976,1:
-443.
Koutinas A, Saridomichelakis M, Polizopoulou Z, Mylonakis M, Leontides L, Bilinis C, Argyriadis D, Diakou N, Papadopoulos O. Improvement of skin lesions in canine leishmaniosis with allopurinol treatment: a randomized, double-blinded, placebo controlled study. Proc 16th Ann cong ESVD-ECVD, 1999, pp. 118.
Slappendel RJ. Visceral leishmaniasis in dogs in Europe. Proc 8th Ann Cong ESVIM, 1998, pp. 95-97.
Persechino A, Oliva G, Ciaramella Ρ, De Luna R, Cortese L. The use of aminosidine in the therapy of leishmaniotic dogs. Riv Zoot Vet, 1994,22:11-16.
Vexenat JA, Olliaro PL, Fonseca de Castro JA, Cavalcante R, Furtado Campos JH, Tavares JP, Miles MA. Clinical recovery and limited cure in canine visceral leishmaniasis
treated with aminosidine (paromomycin). Am J Trop Med Hyg, 1998,58: 448-453.
Berman JD. Experimental chemotherapy of leishmaniasis-a critical review. In: KP Chang, R Bray (Editors) Leishmaniasis. Elsevier Science Publishers BV, Amsterdam, 1985, pp. 111-138.
Lamothe J. Essai de traitement de la leishmaniose canine par Γ amphotericine Β (39 cas). Prat Med ChirurgAnim Comp, 1997,32:133-141.
Lin SH, Medo G, Kobayaski GS, Effects of amphotericin Β on macrophages and their precursor cells. Antimicrob Agents Chemotherapy ,1977,11:154-160.
Bernard E, Quaranta JF, Durant J, Le Fichoux Y, Dellamonica P. Visceral leishmaniasis resistant to conventional treatments: value of amphotericine B. Pathol Biol, 1993,41:817-819.
Lamothe J. Treatment of canine leishmaniasis from A (Amphotericin B) to Ζ (Zyloric). Summaries of Presentations at the International Canine Leishmaniasis Forum, 1999, pp. 4
Lamothe J. A new prospect on canine leishmaniasis: treatment with amphotericine Β (Fungizone). Proc 12th Ann Congr ESVD-ECVD, 1995, pp. 227.
Oliva G, Gradoni L, Ciaramella Ρ, De Luna R, Cortese L, Orsini S, Davidson RN, Persechino A. Activity of liposomal amphotericin Β (AmBisome) in dogs naturally infected with Leishmania infantum. J Antimicrob Chemother, 1995, 36:1013-1019.
Oliva G, Gradoni L, Cortese L, Orsini S, Ciaramella Ρ, Scalone A, De Luna R, Persechino A. Comparative efficacy of meglumine antimonate and aminosidine sulfate, alone or in combination, in canine leishmaniasis. Ann Trop Med Parasitol, 1998, 92:165-171.
Desiderio JV, Rankin BM. Immunomodulators. In: RW Kirk (Editor) Current Veterinary Therapy IX-Small Animal Practice. WB Saunders, Philadelphia, 1986, pp. 1091-1096.
Grant CK, Shelton GH. Biological response modifiers. In: RW Kirk (Editor) Current Veterinary Therapy X-Small Animal Practice. WB Saunders, Philadelphia, 1989, pp. 507-513.
Scott DW, Miller WH, Griffin CE. Dermatologie therapy. In: Müller and Kirk's Small Animal Dermatology, 5th edition. WB Saunders, Philadelphia, 1995, pp. 174-277.
Helton Rhodes K. Feline immunomodulators. In: JD Bonagura (Editor) Current Veterinary Therapy XH-Small Animal Practice. WB Saunders, Philadelphia, 1995, pp. 581-584.
Dorman DC. Neurotoxic drugs in dogs and cats. In: JD Bonagura (Editor) Current Veterinary Therapy XII-Small Animal Practice. WB Saunders, Philadelphia, 1995, pp. 1140-1145.
Ferrer L, Aisa MJ, Roura X, Portus M. Serological diagnosis and treatment of canine leishmaniasis. Vet Ree, 1995,136:514-516.
Bernardina WE, De Luna R, Oliva G, Ciaramella P. An immunodiffusion assay for the detection of canine leishmaniasis due to infection with Leishmania infantum. Vet Parasitol, 1997,73: 207-213.
Vercammen F, De Deken R. Antibody kinetics during allopurinol treatment in canine leishmaniasis. Vet Ree, 1996, 139: 264.
Vercammen F. Evaluating treatment for visceral leishmaniasis. J Am Vet Med Assoc, 1996,209:1379.
Most read articles by the same author(s)